Microsatellite instability is rare in rectal carcinomas and signifies hereditary cancer
Microsatellite instability is rare in rectal carcinomas and signifies hereditary cancer
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DOI：
10.1016/s0959-8049(99)00045-3
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发表时间：
1999-06-01
影响因子：
8.4
通讯作者：
Johnson, A
中科院分区：
文献类型：
--
作者：
Nilbert, M;Planck, M;Johnson, A
我们分析了165例直肠癌的微卫星不稳定性（MSI）。从所有患者中收集个人和/或家族癌症史的数据，并在9例患者中发现异时性癌症，其中2例已发展为结直肠癌，并在3个家庭中发现可疑的结直肠癌家族聚集性。165例直肠癌中只有3例（2%）显示MSI。肿瘤显示MSI的患者的临床病史提示遗传性癌症-结直肠癌和/或同步结直肠癌的家族史。变性梯度凝胶（DGGE）分析被用来筛选MSI+患者的突变hMLH 1和hMSH 2基因，并揭示了两个新的种系突变：1 bp的缺失在外显子10的hMSH 2创建一个过早的终止密码子和剪接供体位点突变在内含子16的hMLH 1。考虑到结直肠癌作为一个组，MSI已被报道发生在约10-20%的肿瘤中，因此本身不能用于遗传性肿瘤的临床检测。然而，这项研究表明，MSI在直肠癌中是罕见的，当存在时，强烈提示结直肠癌发展的遗传易感性。(C)1999 Elsevier Science Ltd.保留所有权利。
We analysed microsatellite instability (MSI) in a consecutive series of 165 rectal carcinomas. Data on a personal and/or family history of cancer were collected from all patients and revealed metachronous cancer in 9 patients, 2 of whom had developed colorectal cancer, and a suspect-ed familial aggregation of colorectal cancer in three families. Only three of the 165 (2%) rectal cancers showed MSI. The patients whose tumours displayed MSI had clinical histories suggesting hereditary cancer-a family history of colorectal cancer and/or synchronous colorectal cancers. Denaturing gradient gel (DGGE) analysis was used to screen the MSI+ patients for mutations in the hMLH1 and hMSH2 genes and revealed two new germline mutations; a 1 bp deletion in exon 10 of hMSH2 creating a premature stop-codon and a splice donor site mutation in intron 16 of hMLH1. Considering colorectal carcinomas as a group, MSI has been reported to occur in approximately 10-20% of the tumours and thus can not, per se be used for clinical detection of hereditary tumours. This study shows, however, that MSI is rare in rectal carcinomas and when present strongly suggests a hereditary predisposition for colorectal cancer development. (C) 1999 Elsevier Science Ltd. All rights reserved.